Hepatitis C virus is rapidly becoming one of the most important infectious health problems and is approaching epidemic status world wide. The CDC estimates that HCV may have already infected more that three million people in the US alone. Treatments for the chronic liver disease that eventually occurs years after HCV infection are limited to interferon and a few experimental antiviral compounds. One of the biggest obstacles to finding new drugs is the lack of a useful culture system for the virus. Dr. Jay Nelson and co-workers have discovered and cultured several new types of human cells that are apparently more permissive for viral replication. Virogenomics has been testing these cells for their ability to support infection and repliction HCV with some encouraging results. The aim of this Phase I project is confirm replication of HCV in activated macrophages or transformed hepatic endothelial cells in culture using a very sensitive TaqMan assay to verify replication by detecting production negative strand RNA. Success in the Phase I part of the project will lead to extended Phase II goals that will aim to create a robust culture system suitable fordrug screening, and look for alterations in gene expression caused by HCV infection through microarray analysis that could yield new host gene targets for blocking the pathogenic effects of the virus.